In order to understand better the early molecular events of normal and abnormal growth, the initial alterations in target cell membranes produced by growth hormones will be studied. We have demonstrated the feasibility of spectroscopically monitoring peptide hormone interactions with plasma membranes utilizing intrinsic spectral parameters and extrinsic fluorescent probes. We propose to extend our studies of how peptide hormones initiate their biological effect by studying the physical interaction of hormones with target cell surfaces and isolated plasma membranes, and to relate this interaction to subsequent biophysical and biochemical events. Growth hormone, glucagon, insulin and their derivatives will be employed with isolated cells and plasma membranes of rat liver and human erythrocyte membranes. Binding of radioiodinated growth hormone will be correlated with changes in circular dichroism and intrinsic fluorescence. A series of fluorescent probes that localize at different regions of the plasma membrane will be used to reveal the effect of hormones on those regions by changes in extrinsic fluorescence. Fluorescent adenosine derivatives will be used to obtain more specific data concerning hormone effects on membrane enzymes. The alteration of plasma membrane enzyme activities by growth hormone will be correlated with changes in spectroscopic properties of the membranes and with growth hormone binding. The influence of calcium, magnesium, and lanthanum on the conformation of membrane components, enzymatic activities and response to hormones will be studied using radioisotopes and tetracycline chelates of these cations.